The present invention relates to ion processing systems and, more particularly, to radio-frequency mass spectrometers and ion storage systems. A major objective of the present invention is to provide flexible apparatus for the processing, storage, and analysis of large numbers of ions in parallel.
Mass spectrometry, or more generally the techniques and apparatus for control and analysis of charged particles or ions, has provided important tools for scientific exploration. Traditionally defined, a mass spectrometer is an instrument which produces ions from one or more substances, sorts these ions into a spectrum according to their mass-to-charge ratios and records the relative abundance of each species of ion present. From its beginnings in the early 1900's, mass spectrometry has become a necessary and integral component of modern science and commerce. Many areas of current research depend upon mass spectrometric techniques to perform crucial experiments. For example, mass spectrometry has found use in the analysis of upper atmospheric gases, detecting and studying ozone depletion processes. Medical research and practice routinely use mass analysis instrumentation for the detailed analysis of protein structures and the genetic coding in DNA. These analytical methods require the precise separation and identification of the mass and quantity of each ion extracted from an initial particle mixture. In many experimental regimes, new laboratory processes rapidly create a large range of molecular species in great quantities, placing ever increasing demands on the rate and fidelity with which mass analysis must occur. Current mass spectrometry technology faces difficult challenges in meeting these experimental needs.
The domain of ion processing encompasses more, however, than just the analytical measurement of distributions of ion mass. Other technologies involve the preparative separation and storage of different ion species. One example would be the separation of isotopes, which vary in atomic mass. The accurate isolation of radioactive isotopes finds use in medicine, nuclear energy and pure physics research. Another use for ion processing techniques involves the separation, buffering and long-term storage of charged antimatter. Most large particle accelerator facilities produce antimatter in the form of anti-protons (positronium) and anti-electrons (positrons). Since the annihilation of matter with antimatter results in the most efficient conversion of matter into energy, extensive efforts are being made, as discussed in report AFRPL TR-85-034, from the University of Dayton Research Institute, toward the trapping, storing and annihilating of positronium. New generations of spacecraft capable of harnessing the energy released in controlled matter-antimatter annihilation could achieve extremely high velocities. Antimatter is highly reactive, however, and must be stored in perfect isolation until final use. The current inability to reliably and effectively cool and store significant quantities of charged antimatter in portable systems is a key factor in preventing practical use of antimatter propulsion. The storage methods used to maintain such antimatter ions comprise another example of potential ion processing techniques.
The explosive growth of mass spectrometric applications throughout science and industry rests on the ability of external and easily controlled electrostatic, magnetostatic and electrodynamic fields to precisely and accurately manipulate charged matter, abilities unequaled by other neutral manipulation techniques. However, all such charged-particle devices suffer from the effects of space charge, that is, mutual coulombic repulsion remains a fundamental physical limit. Yet today, industrial and scientific demands for greater amounts of informative and preparative outputs from smaller samples of matter, and in shorter periods of time, have well exceeded the limits imposed by space charge on device throughput.
All mass spectrometers operate as flow systems. Ions, either captured or created by ionization, are guided through or confined within a volume prior to and during their detection. The mutual coulombic repulsion of like charges, however, makes difficult the production or capture of dense ion fluxes. The maximum output (either in analytical information or in preparative ion production) remains directly proportional to the average number of ions (the ion current) passing through the machine per unit time. The coulombic repulsion from space charge limits this average flow per unit volume. Ultimately, the volume governable by precise ion control limits the throughput of a given device.
Various mass spectrometers, or more generally, tools for the processing, control and analysis of ions, remain currently available. Each device combines unique operation attributes together with particular limitations, suffering more or less from space charge restrictions. Early mass spectrometers were what are now termed magnetic (or magnetic and electrostatic) sector instruments. These devices generally use static magnetic, or magnetic and electric, fields to carefully disperse focused beams of moving charged particles. Depending on the charge-to-mass ratio, the particles' paths bend in different amounts. A mass spectrum for a particle group (that is, a numerical analysis of the mass distribution) comprises measurements taken of the numbers of particles at each focus point.
One form of sector spectrometers disperses the mass spectrum onto a strip of photographic film, forming a mass spectrograph. Photographic means can detect minute components of a substance being analyzed, thus providing a means for accurate mass determination. Photographic techniques, however, are less well suited for relative mass abundance measurements. As an alternative method, then, sector instruments scan their magnetic and/or electric fields such that various masses scan across a narrow stationary slit. Ions passing through this slit can then be detected electronically. The simultaneous photographic approach yields the greatest device throughput; relative abundance measurements through sector scanning are gained at the cost of information through-put. Time-averaging techniques can increase the amount of information collected, but only during relatively short periods due to inherent instabilities in the magnetic and electric confinement fields.
While the sector-type mass spectrometer was one of the earliest instruments in widespread use, it has certain inherent problems. The magnetic fields used to focus the charged particles in one direction tend to defocus ions in the perpendicular direction, requiring further focusing elements. The large magnetic fields required to focus ions often require bulky, heavy and yet precisely machined magnets. As research moves toward larger particle masses (as in biochemical analysis of proteins), the mass ranges of sector instruments must be increased. Yet it is difficult to maintain a highly focused beam over a very wide mass range, thus requiring greater engineering expenditures. A principal drawback of conventional sector mass spectrometers is their expense, in both engineering and fabrication costs.
The changing demands of applied chemistry, physics and medicine have led to radical and innovative changes in all mass spectrometric instrumentation. The diversity of available commercial instruments demonstrates that no single instrument can meet the wide demands of commercial and scientific applications. Sector instruments have in many instances been supplanted by Time-Of-Flight (TOF) mass spectrometers, Fourier Transform Ion Cyclotron Resonance (FT-ICR) devices, Quadrupole spectrometers, triple Quadrupole (Quadrupole-Octupole-Quadrupole), and Ion Trap instruments. These classes of mass spectrometers differ in their approach toward controlling and measuring ion samples (i.e., they have different ion optics), and have particular advantages and disadvantages. The attributes of different devices, including mass range, mass (or energy) resolution, flexibility to detect both positive and negative ions, ion storage, throughput (including scanning rate), dynamic range, ionization methods, simplicity in operation and maintenance, and cost, allow comparisons to be made among them. When other characteristics such as the methods of signal detection, portability, and ease of connection with other equipment are also examined, no single current mass spectrometer device can be best used across a majority of applications.
Time-of-flight (TOF) instruments rely on the fact that ions with equal kinetic energies but with different masses travel with different velocities. Thus, a burst of similarly-energetic ions at one end of a time-of-flight device reach the other end separated in time in a manner related to their respective masses. Time-of-flight mass spectrometers provide excellent resolutions of mass with a very high recording speed, allowing study of fast reactions such as explosions. In addition, the instrumentation is simple and does not necessarily involve complicated magnetic focusing elements.
Problems exist with time-of-flight instruments as well. The total number of ions per initial pulse must usually be limited to prevent a spread in energies by coulombic repulsion, resulting in a loss of mass resolution for the device. In addition, as with the sector devices, the time-of-flight mass spectrometer provides no means for storage or buffering of ions.
One type of device that does provide for ion storage and analysis is an ion cyclotron resonance (ICR) spectrometer. This device (also known as a Fourier Transform ICR (FT-ICR)), uses the principle of a cyclotron. In a cyclotron, a particle can be excited by a high-frequency voltage to move in a spiral, while held within a magnetic field. The angular frequency of motion for the charged particle (the cyclotron frequency) depends upon the magnetic field strength and the mass of the particle. A typical ICR instrument uses an RF voltage to excite ions trapped in a conductive box immersed in the field of a superconducting magnet. The RF voltage is applied to opposing electrode walls of the box. The RF voltage translationally excites the charged particle which, constrained by the magnetic field, moves in a spiral. The ions then orbit on the same radial path, but with different frequencies depending upon their mass. The coherent, orbiting ions induce an image current in another set of detector electrodes. The image current has an amplitude proportional to the number of ions and a frequency proportional to mass, permitting measurement of the relative abundance of ions in a mixture.
Since an ICR device relies on the analogue technique of induction of image currents for measurement of mass, it remains limited in dynamic range. Further, while the instrument exhibits high mass resolution, long acquisition time (due to space charge limitations) and limited information through-put often precludes its use in detection of short-lived ion species, or for events exhibiting rapid real-time fluctuations. Hence, the storage capabilities of the ICR are typically expended for analysis, not for the ion buffering required for large, or high-speed, bursts of ions
Perhaps the most widely used mass spectrometers today rely upon radio-frequency quadrupole techniques. Quadrupole mass spectrometers were first explored by Wolfgang Paul and others in the 1950's, and were the subject of a U.S. Pat. No. 2,939,952. The patent presented two principal types of quadrupole devices. The first device, a quadrupole mass filter, generally comprises four electrode surfaces extending longitudinally in space. The longitudinal direction forms the path for ion travel. The device can be seen in FIG. 1 of the Paul et al patent. Ideally, these electrode surfaces cut hyperbolic arcs through a plane perpendicular to the ion motion and have equal and opposite initial voltages applied to neighboring electrode pairs. Thus, the electrostatic potential around the central ion path is quadratic in form. By multiplying the applied electrode potentials with a periodic function of time, the electric fields at a given point can be made to periodically switch directions. The characteristic motions of ions traveling through the mass filter exist in one of two exclusive states. In the first, stable state, ions perform oscillations about the center of symmetry of fields with amplitudes that are smaller than some critical value. In the second, unstable state, the amplitude of oscillation increases rapidly so that, within a short time, the ions impinge upon the field-generating electrodes and remove, or neutralize, themselves. Given an applied potential and a particular periodic function, ions with certain charge-to-mass ratios travel along a stable path, while ions with other charge-to-mass ratios follow unstable trajectories and are lost. Thus, by varying the amplitude, frequency and DC offset of the voltages that determine the periodic function, certain masses of ions are allowed to pass through the mass filter while others are neutralized.
The equations of motion for a quadrupole mass filter device in the x-y plane perpendicular to the ion trajectory path z are given by: EQU x+(q/mr.sub.0.sup.2).phi.x=0 (1) EQU y-(q/mr.sub.0.sup.2).phi.y=0 (2)
where x and y represent the position of the particle in the plane, q is the charge of the ion, m is the ion's mass, r.sub.0 is the closest distance between the center of the device and a hyperbolic electrode and .phi. is the applied potential function. On injecting ions into the mass filter with a certain velocity in the z direction, Equations (1) and (2) provide the ion motion in the xz and yz planes. If .phi. were merely a constant, all ions would obey paths of simple harmonic motion in the xz plane and ion trajectories would all be "stable", i.e., remain fixed in amplitude. Yet, in the yz plane, the ions would diverge from the z axis (called defocussing) and eventually escape, colliding with the filter electrodes. If, on the other hand, .phi. were a periodic function in time, the trajectories in both planes are alternately deflected toward and away from the central zero point. Stability exists in both planes if the periodicity of the potential function .phi. is short enough and the ion is heavy enough that it cannot respond sufficiently during the defocussing portion of the cycle to escape the device.
In a further modification, if the potential function .phi. combines a direct (or constant) component and a periodic alternating component, light ions are more affected by the alternating component. In the x direction, the light ions would tend to have unstable trajectories whenever the alternating component is larger than the direct component. Ions following unstable trajectories would exhibit oscillations of ever-increasing amplitude. The x direction would therefore provide the equivalent of a high-pass mass filter. Only high masses would be transmitted to the other end of the quadrupole without striking the x electrodes. Simultaneously, in the y direction, heavy ions are unstable because of the defocussing effect of the direct component, but some lighter ions are stabilized by the alternating component if its magnitude and frequency correct the trajectory when the amplitude tends to increase. The y direction is therefore a low-pass mass filter. The two directions together provide a mass filter with a certain pass-band.
When using a mass filter, an ion sample is formed and introduced at one end of the device. Then, while carefully varying the filter's electrical parameters, the quantity of ions emerging at the other end is measured. As discussed, when the function multiplying the applied voltages has both a fixed (time-invariant) component and a periodic component, the device allows only ions within a certain mass range, or pass-band, to have stable paths and emerge for measurement at the output end. The RF amplitude defines the mass stability range for a given DC offset, and ramping the RF amplitude sweeps through a given mass stability range.
The mathematical treatment of ion motion in a quadrupole device, as discussed above, relates the instantaneous motion of an ion with the instantaneous electrostatic field. Another more intuitive visualization of stability in a quadrupole device analogizes a charged ion confined on an instantaneous potential surface to that of a ball rolling on a saddle. As the ball begins to roll down the lower slopes of the saddle, the saddle's surface inverts: what was sloping downhill is now sloping uphill. If the frequency of the inversion is well-chosen, the ball remains trapped indefinitely in the saddle. If trapped in the x-y saddle, a particle traveling through a quadrupole mass filter along the z-axis remains confined within the electrodes and reaches the other end of the device.
Yet another useful conception of quadrupole operation creates a time-average of the instantaneous potential surfaces experienced by a given ion to construct an effective potential surface. Because the ions moving through a quadrupole device move much slower than the quadrupole oscillating fields, the ions experience a time-averaged force that, depending on their charge-to-mass ratios, either keeps them bound or gives them an unstable orbit. A time-averaged potential map for a particle would then show a depression or effective potential well, whose height in energy may either keep a particle bound or allow it an unstable trajectory. The time-averaged effective potential (for a given oscillating field) seen by an ion varies with both its charge and its mass.
An ion trap is the second form of the quadrupole mass spectrometer. The ion trap follows the same general principles as the quadrupole mass filter, but instead of having ions travel along an axis through the device, an ion trap maintains ions at the center of the device cavity. Accordingly, the ion trap takes the hyperboloid form of the electrodes of the mass filter and revolves them about a symmetry axis, forming hyperboloid surfaces of revolution enclosing an inner volume (FIGS. 11 and 12 of the Paul et al patent). Differential voltages applied to neighboring electrode surfaces create a three-dimensional quadrupole field, symmetric about the rotation axis. Again, when a periodic function modulates the applied voltage, the electric fields at a given point within the volume periodically switches directions. Ions caught within the fields are attracted one direction and then the next. As with the mass filter, appropriate selection of the applied modulating function ensures that a field with a pass-band of only a certain range of charge-to-mass ions form stable oscillations within the ion trap. All other combinations follow unstable paths eventually colliding with the electrode cavity walls.
Both the quadrupole mass filter and ion trap have found enormous commercial uses in a variety of scientific and industrial fields. The devices combine sensitivity with adequate resolution in a compact, simple and light-weight apparatus. Especially important benefits are the replacement of cumbersome and expensive magnets with high-speed electronic scanning and linear mass scaling. Still, quadrupole devices entail unique problems. To reproduce quadratic fields within the active device volume, the electrodes must have precise hyperbolic surfaces. Yet it is extremely difficult to machine such surfaces. As a result, mass filter manufacturers often substitute easily manufactured spherical surfaces, which unfortunately introduce errors into the fields and reduce device resolution and precision. In addition, fringing fields from imperfect devices introduce further experimental errors into ion measurements. RF devices are also known to suffer mass discrimination, where the transmission efficiency of particles varies with mass.
As a partial answer to difficult fabrication problems of quadrupole mass spectrometers, alternative methods for duplicating the quadrupole fields have been developed. Arnold, in U.S. Pat. No. 3,501,631, describes methods of replicating quadratic fields by substituting a collection of electrodes held at precisely varied potentials for the single hyperbolic electrodes of a standard quadrupole device. In effect, the second type of quadrupole device imitates the first type. The second type applies potentials to a collection of electrodes in a manner corresponding to the potentials of a quadrupole field. Despite simpler fabrication of electrode surfaces, the long-term stability of the applied potentials (required to duplicate quadrupole action) may offset any economic advantages.
The quadrupole approaches, both the first standard type and the second emulated type, do not completely address the problem of ion separation and control. In quadrupole devices, ions outside the pass-band, those not selected to pass through or stay confined, collide with the outer electrodes, eliminating them from further analysis. In addition, repeated collisions of de-selected ions with the electrodes can create further problems when these adsorbed ions desorb under vacuum, corrupting later samples. While the ion trap allows for storage of ions, it is pulsed, must use a neutral buffer gas, and only a fraction of the stored ions are eventually analyzed, and collisions with buffer gases result in further ion excitation and fragmentation, often changing the observed mass spectrum in unpredictable ways.
While each mass spectrometric approach provides its own benefits and involves its own difficulties, certain general problems persist for all currently-used mass-analytical techniques. The fields used for confining and directing charged particles, whether magnetic as in sector-type and ICR devices, electrostatic as in TOF, or electrodynamic as in quadrupole instruments, all provide generally conservative field environments for the manipulation and analysis of ions. Conservative fields usually are desired, since the total energy of the system, including both the ions and the confining fields, remains constant during the analysis process. The energy continuity provides a high degree of predictability in the experimental process and its resulting spectra. But the constraint that an ion's total energy, both kinetic and potential, remains constant imposes constraints on the fundamental designs of contemporary mass spectrometers.
Because their total energy must usually remain fixed at precise and reproducible levels, the total number of ions that may be processed concurrently is much smaller than the number available in any given sample. To maintain the precise energy levels, the ions must follow spatial paths of small tolerance, in a limited volume. This has two adverse effects. First, the fields that hold ions to the exact paths must be extraordinarily precise, requiring complex, highly-engineered and expensive ion optics. Second, and perhaps more fundamental, space charge effects limit the quantities of ions that may be processed at a given time.
The mutual repulsion of like charges limits the number of same-charge ions that can exist in a given volume of space. The confinement fields counter the space charge repulsion to some extent. But, at greater ion densities ion mutual repulsion overcomes the precise focusing of the ion optics and degrades instrument resolution. To avoid degradation, the number of ions introduced into an instrument must remain below critical limits. But, reducing total ion current reduces the information through-put of the device. For many routine applications, these limits are not significant. Yet, in many other uses, the limitations become severe, especially when attempting measurement of very low abundance ions, and large amounts of the sample must be accumulated before gaining an adequate or meaningful result.
In other applications, it is not the amount of sample available but the time window available for analysis that strains analytic methods. Real-time analysis of atmospheric contaminants may require very rapid mass spectra readings. Mass spectrometers attached to gas chromatography apparatus must analyze ion species from separated peaks as they elute from the chromatograph column. When such peaks follow in rapid succession, analysis time for a given peak may be only a few seconds. If space charge repulsion limits the total number of ions for sampling, reducing through-put and therefore lengthening data sampling time, such high-speed uses may be beyond current mass spectrometric technologies.
An inability to cool ion particles presents a further problem for current mass spectrometer devices. Most spectrometer devices depend upon an initial sample of ions introduced to the device at a somewhat uniform level of energy. However, energetic ion samples often arrive with vastly different energies. Most mass spectrometers handle these particles by simply screening out wrong-energy ions. Other uses for ion processing apparatus, such as storing charge antimatter, depend upon some method for maintaining the kinetic energy of particles within critical limits. Methods of making uniform a collection of ion energies are known as cooling techniques. The conservative fields of current mass spectrometers usually cannot directly cool ions while maintaining their trajectory, since the ion's total energy remains precisely fixed or at worst increases. Thus, researchers deploy other techniques to separately cool ions for subsequent storage or analysis.
One cooling technique introduces a cool neutral gas into the path of the ions. Collisions between the gas and the ions absorbs and makes more uniform the energies of the ion sample. Another cooling technique relies on having each ion induce an image current in an outer conductive wall. The image current can transfer energy from the ion to an external resistance and dissipate it as heat. Application of carefully tuned laser radiation can cool ions, through Doppler-shifting and re-emission effects. However, the required high-power lasers are not yet practical for routine applications such as mass analysis. Another technique involves adiabatic expansion by slowly decreasing the trapping potential, and expanding the trapping volume for the confined particles. The method is equivalent to conventional adiabatic expansion of gases. Any attempt to restore the trapping potential to the original value reheats the confined ions to at least their original energy, if not higher. Stochastic cooling is a variant of image current techniques. In stochastic cooling, electronic feedback monitors the time-coherent motion of ions in storage rings and Penning traps through image current induced at a pick-up electrode. From knowledge of the ion motion, a transient potential applied to a kicker electrode can apply a retarding force for cooling of the coherent collection of ions. The latter method is only useful for coherent groupings of ions, found only in highly specialized applications. None of these cooling techniques allow direct use of the ion confinement fields to cool incoherent groups of ions, while maintaining their trajectory.
None of the methods discussed for mass spectrometry or for ion storage and manipulation provides a complete and flexible system for ion processing. What is needed is an improved method and system for the processing, control and analysis of ions. An improved ion processing system should routinely handle very large samples of ions that, due to space charge limitations, are beyond the capacity of current ion optics. In addition, the method and system should be able to store temporally, or buffer, high-volume bursts of ions for later processing. The method should provide for non-destructive spatial separation of ion species to allow complete analysis of an ion sample, and simultaneously provide an efficient tool for ion/isotope separation. Further, the method should provide cooling for stored ions without the use of neutral gases, laser radiation or any means other than the confining fields themselves. Ideally, the method should allow instrumental access to trapped charged particles, providing feedback to monitor operational status in real time. The method should provide a simple and cost-effective technology for translating, storing, cooling and analyzing ion particles.